20-10216813-A-T

Variant names:

• chr20-10216813-A-T
• rs6077690
• ENST00000421143.7:n.133-19876T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000451151.7(SNAP25-AS1):​n.301+2424T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,468 control chromosomes in the GnomAD database, including 20,672 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20672 hom., cov: 29)
• Consequence: SNAP25-AS1 ENST00000451151.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.26
• Publications: 9 publications found

Genes affected

SNAP25-AS1 (HGNC:44312): (SNAP25 antisense RNA 1)

SNAP25 (HGNC:11132): (synaptosome associated protein 25) Synaptic vesicle membrane docking and fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs). The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, one of which is supplied by v-SNARE and the other three by t-SNARE. For t-SNAREs on the plasma membrane, the protein syntaxin supplies one helix and the protein encoded by this gene contributes the other two. Therefore, this gene product is a presynaptic plasma membrane protein involved in the regulation of neurotransmitter release. Two alternative transcript variants encoding different protein isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

SNAP25 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
• congenital myasthenic syndrome 18

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• presynaptic congenital myasthenic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000305058 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000451151.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25-AS1	NR_040710.1		n.270+2424T>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNAP25-AS1	ENST00000421143.7	TSL:5	n.133-19876T>A		intron	N/A
	SNAP25-AS1	ENST00000426491.5	TSL:5	n.270+2424T>A		intron	N/A
	SNAP25-AS1	ENST00000451151.7	TSL:2	n.301+2424T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77711 AN: 151350 Hom.: 20663 Cov.: 29

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.513 AC: 77745 AN: 151468 Hom.: 20672 Cov.: 29 AF XY: 0.518 AC XY: 38304 AN XY: 73966

African (AFR) AF: 0.353 AC: 14538 AN: 41234

American (AMR) AF: 0.631 AC: 9606 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3468

East Asian (EAS) AF: 0.520 AC: 2666 AN: 5128

South Asian (SAS) AF: 0.539 AC: 2577 AN: 4784

European-Finnish (FIN) AF: 0.583 AC: 6087 AN: 10440

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.564 AC: 38268 AN: 67894

Other (OTH) AF: 0.560 AC: 1181 AN: 2108

Alfa AF: 0.530 Hom.: 2714

Bravo AF: 0.513

Asia WGS AF: 0.542 AC: 1883 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.79
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6077690;

hg19: chr20-10197461;